PROJECT SUMMARY: Longitudinal Study of Endocrine-Disrupting Chemical Exposure and the Early Hormonal Milieu of Girls Around the Time of Thelarche Endocrine disrupting chemicals (EDCs) are exogenous substances which exhibit hormonal activity in the endocrine system, disrupting the physiologic function of endogenous hormones. The peri-pubertal period represents a developmental window of vulnerability to environmental exposures in which EDCs may act as agonists or antagonists to endogenous hormones. Evidence directly linking EDCs and alterations in pubertal development in human populations is far from conclusive. Evidence directly linking exposure to EDCs and changes in serum steroid hormone levels in girls around the time of breast development is almost non-existent. Previous studies of pubertal girls (both in our cohort and others) have reported that exposure to certain EDCs is associated with either later or earlier thelarche and menarche suggesting that EDCs may have an effect on the hormonal milieu in pubertal girls. None of these studies has examined whether a mixture of environmental exposures is related to age at pubertal events. Knowledge about the structural relationship regarding the direct effect of EDCs on hormone levels in girls and then the timing and intensity of later pubertal events, such as age at thelarche, age at menarche, pubertal tempo, peak height velocity, and age at peak height, is lacking. With the measurement of multiple environmental biomarkers in our cohort of girls, we can develop metrics for mixtures of environmental exposures and use these metrics in our analyses. With our prospective study design including direct observation of pubertal maturation events and measurements of steroid hormones in serum around the time of thelarche, we can examine the effect of exposure to EDCs on these events using structural equation models. Our study proposes to fill the gap in knowledge regarding whether exposure to EDCs has a direct effect on the hormonal milieu in pubertal girls, and how these changes in are related to age at pubertal milestones. This application is highly innovative because of its unique design: girls have been evaluated longitudinally from ages 6-7 years, with serum hormone measurements during time points around thelarche, and measurements of environmental biomarkers prior to puberty. Our hypotheses are novel. Using existing prospectively collected pubertal maturation and environmental biomarker data, and recently acquired measurements of serum hormones in banked serum samples timed to maturation events, in a group of girls followed since ages 6 and 7, we will directly addresses the gaps noted in the 2013 IBCERCC report ?Breast Cancer and the Environment: Prioritizing Prevention?. The impact of this proposal is to provide information that will lead to the identification of mechanisms of EDCs and targetable pathways, resulting in strategies to minimize disruption in the timing of pubertal events in girls and future risk of adverse health outcomes in adult women.